PURPOSE: This proposal addresses how a balance between excitation and inhibition is maintained in cortical circuits during gamma oscillations. Specifically, I will determine the relationship between excitatory and inhibitory synaptic currents during rapidly modulated gamma oscillations. This study is performed in the hippocampus both in vivo and in vitro, using intracellular and extracellular electrophysiological recordings. BACKGROUND: Gamma oscillations, the synchronous spiking of neurons at frequencies of 20-80Hz, are believed to play a crucial role in the processing of sensory information. In vivo recordings from cortical areas have shown that gamma oscillations are evoked by sensory stimuli. In fact, the frequency and amplitude of these oscillations are modulated by the nature of the stimulus and the locus of attention. These ongoing changes in the firing frequency and number of neurons participating in oscillations produce rapidly changing patterns of synaptic activity. Balanced changes in excitatory and inhibitory synaptic activity determine the computations performed by cortical neurons and are a critical characteristic of cortical network stability. It is not known, however, how cortical networks of neurons maintain a balance between excitation and inhibition during this rapidly modulated gamma oscillations. Aim 1: Determine the relationship between excitatory and inhibitory currents during the modulation of gamma oscillation amplitude. Using simultaneous field and whole cell patch-clamp recordings in the hippocampus both in vivo and in vitro, I will test the hypothesis (I) that: inhibitory currents dynamically balance excitatory currents during modulated gamma oscillation amplitude. Aim 2: Determine the mechanisms underlying the modulation of gamma oscillation frequency. Using simultaneous field and whole cell patch-clamp recordings in the hippocampus both in vivo and in vitro, I will test the hypothesis (II) that: fluctuations in the amplitude of inhibitory synaptic currents modulate oscillation frequency by regulating the interval between individual oscillation cycles. PUBLIC HEALTH RELAVANCE: By establishing how inhibitory circuits rapidly balance changes in excitation, this study will elucidate the mechanisms that enable the cortex to robustly operate over a broad range of excitatory stimuli. A deeper understanding of the factors that regulate cortical excitability may contribute to the development of therapies aimed at preventing epileptogensis in cortical areas.